Abstract
Fungal polyketides are natural products with great chemical diversity that exhibit a wide range of biological activity. This chemical diversity stems from specialized enzymes encoded in the biosynthetic gene cluster responsible for the natural product biosynthesis. Fungal polyketide synthases (PKS) are the megasynthases that produce the carbon scaffolds for the molecules. Subsequent downstream tailoring enzymes such as oxygenases will then further modify the organic framework. In fungi, many of these enzymes have been found to work iteratively-catalyzing multiple reactions on different sites of the substrate. This perspective will analyze several examples of fungal polyketides that are assembled from a scaffold-building iterative PKS and an accompanying iterative tailoring oxygenase. In these examples, the PKS product is designed for downstream iterative oxygenations to generate additional complexity. Together, these iterative enzymes orchestrate the efficient biosynthesis of elaborate natural products such as lovastatin, chaetoglobosin A, cytochalasin E, and aurovertin E.